Congestive heart failure, regardless of its etiology, is characterized by a weakness of the myocardial tissue of the left and/or right ventricle of the heart to pump and circulate blood into systemic and/or pulmonary circulations. It is accompanied by circulatory and neurohumoral changes which result in failure to deliver sufficient blood and oxygen supply to peripheral tissues and vital organs. If left untreated, the health of a patient with congestive heart failure could progress to the point where the disease would be fatal.
Amlodipine, 3-ethyl-5-methyl-2-(2-aminoethoxymethyl)4-(2-chlorophenyl)-1,4-dihydro-6-m ethylpyridine-3,5-dicarboxylate, and its pharmaceutically acceptable acid addition salts are calcium channel blockers known for their effectiveness in the treatment, inter alia, of congestive heart failure, see U.S. Pat. No. 5,155,120 to Lazar et al. Amlodipine is currently marketed as the besylate salt.
Felodipine, .+-.ethyl methyl-4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate, is also a calcium channel blocker. It is disclosed in U.S. Pat. No. 4,264,611 to Berntsson et al. and is currently marketed as the free base.
ACE inhibitors are well known in the art for their activity in inhibiting angiotensin converting enzyme, thereby blocking conversion of the decapeptide angiotensin I to angiotensin II. The principal pharmacological and clinical effects of ACE inhibitors arise from suppression of synthesis of angiotensin II. Angiotensin II is a potent pressor substance and, therefore, blood pressure lowering can result from inhibition of its biosynthesis, especially in animals and humans whose hypertension is angiotensin II related. ACE inhibitors are effective antihypertensive agents in a variety of animal models and are clinically useful for the treatment of hypertension in humans.
ACE inhibitors are also employed for the treatment of heart conditions such as angina. It is known that at least some ACE inhibitors can improve (i.e., decrease) morbidity and mortality in patient populations with heart conditions.
International application PCT/US92/03873, published as WO 92/20342, discloses pharmaceutical compositions containing a combination of an angiotensin II antagonist and a calcium channel blocker for use in the treatment of hypertension and congestive heart failure. The publication states that the particular compositions can further contain antihypertensives and/or diuretics and/or angiotensin converting enzyme inhibitors.